The effect of tyrosine kinase inhibitor genistein on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.
We examined the effect of the protein tyrosine kinase (PTK) inhibitor, genistein on voltage-dependent K+ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells, using whole-cell patch clamp techniques. The amplitude of the Kv current was inhibited by genistein in a dose-dependent manner, with a Kd value of 7.51 microM. Genistein had no effect on the steady-state activation or inactivation of Kv channels. The applications of trains of pulses at 1 or 2 Hz caused a progressive increase in the genistein-blockade. Genistein produced use-dependent inhibition of the Kv currents, consistent with a slow recovery from inactivation in the presence of genistein. Daidzein and genistin, two inactive analogs of genistein, showed an inhibitory effect similar to that of genistein on Kv channels. Moreover, the absence of ATP inside the pipette did not influence the blocking effect of genistein. We suggest that genistein directly inhibited the Kv current, independently of PTK inhibition.
Ko
Eun A
EA
National Research Laboratory for Mitochondrial Signaling, FIRST Mitochondria Research Group, Department of Physiology and Biophysics, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Republic of Korea.
Park
Won Sun
WS
Son
Youn Kyoung
YK
Kim
Do Hyung
DH
Kim
Nari
N
Kim
Hyoung Kyu
HK
Choi
Tae-Hoon
TH
Jung
In Duk
ID
Park
Yeong-Min
YM
Han
Jin
J
D000818:Animals; D003331:Coronary Vessels / Q000166:cytology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019833:Genistein / Q000494:pharmacology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011817:Rabbits
D024642:Potassium Channels, Voltage-Gated; D047428:Protein Kinase Inhibitors; D019833:Genistein; D011188:Potassium